ABSTRACT Walking is a core activity of human life. Mobility limitation, or difficulty or inability to walk, can limit a person's ability to work, live independently, and participate in the community. Heart and brain health are two of the strongest modifiable pathways to mobility limitation. African Americans have a disproportionate burden of cardiovascular disease (CVD), cerebrovascular disease (CBVD), cognitive impairment, and mobility limitation, but the majority of research on the relationship between these conditions has been conducted in predominantly white populations. The biology and optimal prevention strategies for mobility limitation may differ by race/ethnicity, highlighting a critical need for research in underrepresented populations. The proposed research will add validated measures of mobility, disability, and physical performance to the Jackson Heart Study (JHS), a cohort study of African Americans, designed to investigate causes of CVD in a high-risk population. JHS participants have undergone three exams (Exam 1, 2000-2004, Exam 2, 2005-2008, Exam 3, 2009-2013); Exam 4 is scheduled on the 3,500 remaining participants (mean age = 65 years) beginning in 2020. The exam will include extensive CVD measures, socioeconomic status, psychosocial health, cognitive testing, and brain MRI. We propose an ancillary study to add established measures of mobility limitation: gait speed <0.6 m/s, and self-reported difficulty/inability to walk a quarter of a mile or climb 10 stairs. We will leverage the nearly 20 years of data on CVD/CBVD risk factors and newly collected data on subclinical vascular disease and brain health to better understand the timing of exposure to risk factors and mediating pathways to mobility limitation in African Americans. We hypothesize that exposure to high blood pressure, high fasting glucose, and adiposity in midlife will have stronger associations with mobility limitation in older adults than exposure to these risk factors in late life. We will use novel statistical mediation methods to quantify the extent to which potential mediators explain the relationship between CVD/CBVD risk factors and mobility limitation, while allowing us to test for potential interactions by these mediators. This research will support our long-term goal to enhance functional health among African Americans, in order to preserve independence and participation in the community. Understanding the link between heart and brain health and mobility limitation is critical to reduce racial disparities in health. Moreover, the addition of the functional measures will help expand JHS into a contemporary study cardiovascular health and aging in African Americans.